Antiviral Treatment of Herpes Simplex Virus Decreases the Risk of Alzheimer's Disease and Dementia

Background: Alzheimer’s disease (AD) and dementia create major global health and economic burdens. Herpes simplex virus (HSV) infects over 3 billion people, and chronic infection is increasingly linked to neurodegeneration. Objectives: To evaluate whether antiviral therapy for oral, mucocutaneous, or anogenital HSV lowers the subsequent risk of AD and dementia. Methods: A retrospective cohort study with propensity-score matching was performed in the TriNetX Research Network. On 24 May 2024, 615,324 individuals with HSV were identified; those with prior AD, intracranial injury, or cerebral infarction were excluded. Matching balanced age, sex, race, body-mass index, smoking, diabetes, hypertension between antiviral-treated and untreated groups. Therapies included acyclovir, valacyclovir, penciclovir, ganciclovir, valganciclovir, and famciclovir. Incidences of AD and dementia were identified by ICD-10 codes, and relative risks (RR) with 95% confidence intervals (CI) were calculated. Results: After matching, 231,277 patients per cohort (mean age 36.8 y; 67.7% female) were analyzed. Antiviral treatment for oral/ mucocutaneous HSV significantly reduced the risk of AD (RR 0.87; 95% CI 0.73-0.92) and dementia (RR 0.83; 95% CI 0.77-0.90). No significant association was observed for anogenital HSV. Conclusions: Antiviral therapy for oral or mucocutaneous HSV was associated with a 13% to 17% reduction in risk for AD and dementia. These findings suggest that early antiviral management of HSV infections may represent a feasible preventive strategy against neurodegenerative disease, meriting prospective confirmation.